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Nadine Mothes

Publications and source records attributed to Nadine Mothes.

7 recordsLinked to original sources

Allergy testing: the role of recombinant allergens.

Currently, diagnosis of type I allergy is performed using crude allergen extracts, which allow the identification of the allergen-containing source responsible for type I allergic symptoms (e.g., allergic rhino-conjunctivitis, asthma) but not the disease-eliciting molecules. With the introduction of recombinant allergens produced by molecular biology techniques, a large panel of allergenic molecules has become available. The application of these recombinant allergens for in vitro tests has led to new forms of component-resolved diagnosis (CRD) and allows the establishment of a patient's individual reactivity profile. The increasing number of recombinant allergens characterized during the last decade has allowed the development of chip-based allergy tests for simultaneous detection of up to 5000 different allergens and epitopes. The introduction of these recombinant allergen-based tests into clinical practice improves the selection of patients for traditional specific immunotherapy and allows monitoring of the immunological efficacy of specific immunotherapy by measuring allergen-specific IgG antibodies. Besides their diagnostic application, recombinant allergens and hypoallergenic derivatives thereof have also been used as vaccines in clinical trials, and recent results have shown their usefulness for the treatment of type I allergy.

Allergens↗

Characterization of wild-type recombinant Bet v 1a as a candidate vaccine against birch pollen allergy.

BACKGROUND: We describe the production in Escherichia coli as a recombinant protein of clinical grade wild-type Bet v 1a (rBet v 1a), to be used as a candidate vaccine against birch pollen allergy. METHODS: This recombinant protein was purified by hydrophobic interaction and ion exchange chromatography and characterized by SDS-PAGE, immunoprint and circular dichroism in parallel with natural Bet v 1 (nBet v 1) purified from a birch pollen extract. We also compared rBet v 1 and nBet v 1 for their capacity to induce histamine release from basophils and to stimulate T lymphocyte proliferation. RESULTS: rBet v 1a appears in SDS-PAGE as an 18-kDa monomeric protein, whereas purified nBet v 1 comprises a mixture of isoforms (resolving as three distinct bands and six spots after 1-dimensional and 2-dimensional electrophoresis, respectively). Both recombinant and natural purified Bet v 1 molecules are recognized by IgE from birch pollen-allergic patients as well as anti-Bet v 1 murine monoclonal antibodies, suggesting that the recombinant protein is correctly folded in a native configuration. Circular dichroism analysis confirmed that the two Bet v 1 molecules exhibit similar 3-dimensional structures, even if rBet v 1a appears more compact and stable in thermodenaturation/renaturation experiments. Both rBet v 1 and nBet v 1 induce the degranulation of sensitized basophils and proliferation of Bet v 1-specific T lymphocytes in a similar manner. CONCLUSIONS: On the basis of these structural and biological properties, rBet v 1a is a valid candidate vaccine against birch pollen allergy, currently evaluated in humans.

Allergens↗

Transition from a botanical to a molecular classification in tree pollen allergy: implications for diagnosis and therapy.

Tree pollens are among the most important allergen sources. Allergic cross-reactivity to pollens of trees from various plant orders has so far been classified according to botanical relationships. In this context, cross-reactivities to pollens of trees of the Fagales order (birch, alder, hazel, hornbeam, oak, chestnut), fruits and vegetables, between pollens of the Scrophulariales (olive, ash, plantain, privet, lilac) and pollens of the Coniferales (cedar, cypress, pine) are well established. The application of molecular biology methods for allergen characterization has revealed the molecular nature of many important tree pollen allergens. We review the spectrum of tree pollen allergens and propose a classification of tree pollen and related allergies based on major allergen molecules instead of botanical relationships among the allergenic sources. This molecular classification suggests the major birch pollen allergen, Bet v 1 as a marker for Fagales pollen and related plant food allergies, the major olive pollen allergen, Ole e 1, as a possible marker for Scrophulariales pollen allergy and the cedar allergens, Cry j 1 and Cry j 2, as potential markers for allergy to Coniferales pollens. We exemplify for Fagales pollen allergy and Bet v 1 that major marker allergens are diagnostic tools to determine the disease-eliciting allergen source. Information obtained by diagnostic testing with marker allergens will be important for the appropriate selection of patients for allergen-specific forms of therapy.

Allergens↗

Biology of tree pollen allergens.

More than 25% of the population suffer from type I allergy. Pollens from trees of the Fagales, Oleaceae, and Cupressaceae belong to the most potent and frequent allergen sources. During the past 15 years, the nature of the most important allergens has been identified by molecular biological techniques, and recombinant allergens equivalent to the natural allergens have been produced. These advances provide insight into the biological functions of important allergens and allow the development of novel forms of diagnosis and therapy. In this review, we focus on Fagales allergens to illustrate the impact of recombinant allergens on diagnosis and therapy. We discuss structural similarities as a molecular basis for cross-reactivities and develop diagnostic concepts by using species-specific marker allergens as well as highly cross-reactive allergens. The identification of the allergen recognition profiles of patients with recombinant allergens allows a more precise selection of patients for available forms of allergy treatment. Moreover, we describe novel recombinant allergen-based forms of specific immunotherapy.

Allergens↗

Autoimmunity and atopic dermatitis.

PURPOSE OF REVIEW: It has been demonstrated that a considerable percentage of patients suffering from atopic dermatitis mount IgE autoantibodies against a broad variety of human proteins. This review summarizes evidence for autoimmune mechanisms in atopic dermatitis and suggests novel pathomechanisms that may be involved in this disease. RECENT FINDINGS: It has been shown that patients suffering from atopic dermatitis exhibit IgE autoreactivity to human proteins. These autoantigens are expressed in a variety of cell and tissue types. Complementary DNAs coding for IgE autoantigens have been identified, cloned and characterized at the molecular level. Using purified recombinant IgE autoantigens, it has been shown in paradigmatic models that IgE autoimmunity may be a pathogenetic mechanism in atopic dermatitis. Moreover, it has been shown that the levels of IgE autoantibodies are associated with severity of disease. SUMMARY: Patients suffering from severe manifestations of atopy mount IgE autoantibodies against a variety of human proteins. The levels of IgE autoantibodies correspond with disease severity. Several mechanisms of IgE autoimmunity may contribute to the pathogenesis of atopic dermatitis.

Allergens↗